Enhanced x-ray angiography analysis and interpretation using deep learning Over 1 Million diagnostic X-ray angiograms are performed annually in the US to guide treatment of coronary artery disease (CAD) and cost over $12 billion. Despite being the clinical standard of care, visual interpretation is prone to inter- and intra-observer variability. Recently as part of the NHLBI supported Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, our research team showed that cardiologists misinterpreted over 19% of angiograms obstructive CAD (greater than 50% vessel stenosis). Given the centrality of angiographic interpretation to the development of a treatment plan, reduced accuracy can lead to unnecessary poor outcomes and increased costs to our healthcare system. The potential impact is significant given that increasing interpretation accuracy by 1% could positively benefit over 10,000 patients each year in the US alone. Thus, our team is developing an X-ray angiographic analysis system (DeepAngio) driven by deep learning technology to enhance physician interpretation. In Phase I, the PROMISE dataset of over 1,000 angiograms was used to build our Convolutional Neural Network (CNN) based deep learning model. We achieved a 0.89 Area Under the Receiving Operating Characteristic (AUROC) for identifying obstructive CAD in images with expert scored ground truth (exceeding our proposed Phase I milestone of >0.85 AUROC). Now in Phase II, we present an innovative image learning pipeline to incorporate anatomical and spatiotemporal information from video sequences (similar to a cardiologist reader). A full end to end X-ray angiography video processing pipeline will be developed and tested in a new cohort of 10,000 patient angiograms with normal and graded abnormal CAD. Our patch-based frame analysis model will advance to CNN full frame-based classification of angiographic views (left heart vs. right heart) and segmentation of coronary vessels (LAD, LCx, and RCA). A multiple frame analysis approach enabled by a Recursive Neural Network (RNN) will equip our model with dynamic temporal information to estimate lesion presence accurately. Our goal for Phase II is to improve reading specificity and translate our Phase I proof of concept research findings into a clinically meaningful tool. A multi-reader, multi-case evaluation by a group of interventional cardiologists interpreting with and without DeepAngio predictions will assess clinical usability to improve coronary stenosis estimation. In the long term, we hope the combination of a cardiologist with DeepAngio as an assistive tool will improve the clinical accuracy of angiographic interpretation.